Abstract
BackgroundGastric cancer is one of the most common malignant tumors of the digestive system. However, its targeted therapy develops at a slow pace. Thus, exploring the mechanisms of the malignant behavior of gastric cancer cells is crucial to exploit its treatment. Mammalian never-in-mitosis A (NIMA)-related kinases (NEKs) are considered to play a significant role in cancer cell proliferation. However, no study has reported on NIMA family proteins in gastric cancer.MethodsBioinformatics analysis was employed to clarify the expression patterns of NEK1–NEK11 and their effects on prognosis. The effects of NEK7 on immune infiltration and NEK7 related pathways were also analyzed. At the cell level, 5-ethynyl-2-deoxyuridine, cell cycle, and Cell Counting Kit-8 assays were utilized to clarify the effect of NEK7 on gastric cancer cell proliferation. A mouse subcutaneous model revealed the regulating effect of NEK7 on gastric cancer cell proliferation in vivo.ResultsBioinformatics analysis revealed that NEK7 is upregulated in gastric cancer and is related to poor prognosis. NEK7 is also related to T-stage, which is closely associated with cell proliferation. Further analysis showed that NEK7 was correlated with infiltration of multiple immune cells as well as gastric cancer-related pathways. Cell experiments indicated the promoting effect of NEK7 on cell proliferation, while the absence of NEK7 could lead to inhibition of gastric cancer proliferation and G1/S arrest.ConclusionNEK7 exerts a regulatory effect on cell proliferation and is closely related to tumor immune infiltration.
Highlights
Gastric cancer is one of the most common malignant tumors of the digestive system
NEK7 is highly expressed in gastric cancer cells and may be implicated in poor prognosis We synthetically analyzed the expression of never-in-mitosis A (NIMA) kinases (NEK1–NEK11) (Fig. 1a–k) in gastric cancer tissues and normal tissues
The results showed that only the expression level of NEK7
Summary
Gastric cancer is one of the most common malignant tumors of the digestive system. Exploring the mechanisms of the malignant behavior of gastric cancer cells is crucial to exploit its treatment. Mammalian never-in-mitosis A (NIMA)-related kinases (NEKs) are considered to play a significant role in cancer cell proliferation. No study has reported on NIMA family proteins in gastric cancer. The stability of the cell cycle is maintained by many regulatory proteins, especially by kinases [2]. Abnormal expression of cell cycle-related kinases could accelerate the cell cycle and result in inappropriate proliferation. Mammalian never-in-mitosis A (NIMA)-related kinases (NEK proteins) are a group of positive regulatory proteins of the cell cycle that could regulate microtubules and promote mitosis. Expressions of NEK proteins are higher in various malignant tissues than in normal tissues
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